Amblyopia is a developmental disorder of spatial vision usually associated with the presence of strabismus, anisometropia or form deprivation early in life. It affects visual acuity, contrast sensitivity and position acuity. Amblyopia is cliically important because, aside from refractive error, it is the most frequent cause of vision loss in infants and young children. It is of basic interest because it reflects the neural impairment that can occur when normal visual development is disrupted. The long-range objectives of this research are to understand the mechanisms that limit spatial vision in humans with amblyopia, with the ultimate goal of developing new approaches aimed at more effective treatment. Although amblyopia is thought to reflect alterations in the neuronal properties of cortical area V1, recent work suggests that amblyopes may have: abnormal crowding, higher-level neural deficits, reduced sampling efficiency, increased multiplicative cortical noise, and previously unsuspected amounts of neural plasticity. We propose a number of innovative methods that will enable us to assess the limits and mechanisms of neural plasticity in adults and children with amblyopia. Aim 1. Aim 1. Neural Plasticity: boosting the efficacy of Perceptual Learning in amblyopic vision. There is a surprising degree of neural plasticity in both normal and amblyopic adults as evidenced by Perceptual Learning (PL). A major goal of this proposal is to try to increase the effects of PL by: i) making PL more effective (stronger) using the cholinesterase inhibitor donepezil to increase the synaptic levels of Acetylcholine (Ach) in the brain, and thereby increase plasticity in the amblyopic visual system. ii) making PL more general using a novel quadruple training paradigm, and iii) extending PL to children with amblyopia. Aim 2. Crowding and uncrowding in amblyopic vision. Crowding (the impaired identification of a target among other targets) is the main bottleneck for object recognition and reading in peripheral and amblyopic vision. i) We propose a series of experiments, using novel methods and modeling, to test among several hypotheses for amblyopic crowding: suppression, abnormal feature integration, feature substitution. ii) We will test the hypothesis that crowding i amblyopia can be alleviated through Perceptual Learning (PL), and that alleviating crowding will result in improved acuity and reading speed in amblyopia. Aim 3. Binocular Combination and recovery of binocular vision and stereopsis in amblyopia. We propose novel methods for measuring and modeling the rules governing binocular combination and stereopsis in individuals with strabismus and amblyopia. We propose to test several hypotheses regarding this combination, specifically: i) that fusion and stereopsis require balanced input to the two eyes, and ii) that binocularity and stereopsis can be substantially recovered through perceptual learning. iii) We will characterize and quantify the recovered stereopsis. An important goal is to examine whether the recovery is due to changes in fusional vergence, sensory fusion or both. PUBLIC HEALTH RELEVANCE: Amblyopia is a developmental disorder of spatial vision usually associated with the presence of strabismus, anisometropia or form deprivation early in life. It is the most frequent cause of permanent vision loss in infants and young children, and it reflects the neural impairment that can occur when normal visual development is disrupted, and is thus an ideal model for understanding when and how brain plasticity may be harnessed for recovery of function. Our goal is to assess the limits and mechanisms of neural plasticity in the spatial vision of adults and children with amblyopia.